Coexistence of low levels of HBsAg and high levels of anti-HBs may increase risk of hepatocellular carcinoma in chronic hepatitis B patients with high HBV load

Jin, Zi-zheng; Jin, Fangfang; Liu, Xin; Liu, Ning; Wen, Feng; Lou, Jinli

doi:10.1016/j.bjid.2019.08.007

Cited by 11 publications

(10 citation statements)

References 21 publications

(26 reference statements)

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“…Mutations in other regions such as polymerase, core, X and presurface regions have also been implicated in this phenomenon of coexistence of HBsAg and anti-HBs [54,56–58]. Coexistence of HBsAg and anti-HBs has been linked to increased disease progression [49,59]. In this study, we only amplified a portion of the surface gene, so the potential cause of mutations for the coexistence of the HBsAg and anti-HBs cannot be ruled out.…”

Section: Discussionmentioning

confidence: 98%

Decreased hepatitis B virus vaccine response among HIV-positive infants compared with HIV-negative infants in Botswana

Shaver

Anderson

Bhebhe

et al. 2022

Aids

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Section: Discussionmentioning

confidence: 98%

Decreased hepatitis B virus vaccine response among HIV-positive infants compared with HIV-negative infants in Botswana

Shaver

Anderson

Bhebhe

et al. 2022

Aids

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“…Characteristics in HBsAg/anti-HBs coexistence such as age over 50 years and abnormal ALT levels were also risk factors for HCC, which was linked to a long history of HBV infection with advanced liver fibrosis and active inflammation [29,72]. Serum PIVKA-II, better correlated with portal vein invasion, larger tumor size and recurrence of HBV-associated HCC [73], was also observed with higher levels in coexistence group [69].…”

Section: Clinical Characteristics and Advanced Liver Diseases In Coexmentioning

confidence: 96%

“…However, the higher prevalence rates (21%) were obtained in Japan and Singapore in 1996, which might overestimate the occurrence of concurrent HBsAg/anti-HBs due to limited sample size and inclusion of acute HBV infection. The coexistence of HBsAg and anti-HBs might be associated with important clinical concerns and this profile could be linked to advanced fibrosis, hepatocellular carcinoma (HCC) and liver failure [69]. Among 92 patients with simultaneous HBsAg/anti-HBs occurrence in Korea, 6.5% suffered from liver cirrhosis and 2.2% were diagnosed with HCC [70].…”

Section: Clinical Characteristics and Advanced Liver Diseases In Coexmentioning

confidence: 99%

Paradoxical HBsAg and anti-HBs coexistence among Chronic HBV Infections: Causes and Consequences

Jiang¹,

Chang²,

Yan³

et al. 2021

Int. J. Biol. Sci.

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Hepatitis B surface antigen (HBsAg) and Hepatitis B surface antibody (anti-HBs) were reported simultaneously among Hepatitis B virus (HBV) infections. HBsAg is a specific indicator of acute or chronic HBV infections, while anti-HBs is a protective antibody reflecting the recovery and immunity of hosts. HBsAg and anti-HBs coexist during seroconversion and then form immune complex, which is rare detected in clinical cases. However, with the promotion of vaccination and the application of various antiviral drugs, along with the rapid development of medical technology, the coexistence of HBsAg and anti-HBs has become more prevalent. Mutations in the viral genomes, immune status and genetic factors of hosts may contribute to the coexistence. Novel HBsAg assays, with higher sensitivity and ability to detect mutations or immune complexes, can also yield HBsAg/anti-HBs coexistence. The discovery of coexistence has shattered the idea of traditional serological patterns and raised questions about the effectiveness of vaccines. Worth noting is that HBsAg/anti-HBs double positivity is strongly associated with progressive liver diseases, especially hepatocellular carcinoma. In conclusion, viral mutations, host factors, and methodology impacts can all lead to the coexistence of HBsAg and anti-HBs. This coexistence is not an indicator of improvement, as an increased risk of adverse clinical outcomes still exists.

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“…Theoretically, the simultaneous presence of both positive hepatitis B surface antigen (HBsAg) and HBsAb in circulation should not appear in the same patient. However, this understanding has been challenged by several studies indicating the HBsAg+/HBsAb+ in chronic HBV patients from 2.63% to 8.9% (7)(8)(9)(10)(11). The mechanism underlying the simultaneous presence of HBsAg and HBsAb remains unclear and even controversial.…”

Section: Introductionmentioning

confidence: 99%

“…The mechanism underlying the simultaneous presence of HBsAg and HBsAb remains unclear and even controversial. Moreover, concurrent HBsAg and HBsAb also increased the risk for the development of HCC in CHB ( 8 , 12 ). Therefore, it is necessary to investigate the clinical as well as biological implications of HBsAg+/HBsAb+ serological profile, which might help in the precise clinical management such as proper therapeutic interventions and disease monitoring in HBV-related diseases ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing

et al. 2021

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BackgroundThis study aimed to explore the molecular mechanism of the coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (HBsAb) serological pattern via intensive characterization of HBV s gene in both chronic hepatitis B (CHB) and hepatocellular carcinoma (HCC) patients.MethodA total of 73 HBsAg+/HBsAb+ patients (CHB = 36, HCC = 37) and 96 HBsAg+/HBsAb− patients (CHB = 47, HCC = 49) were enrolled from 13 medical centers in China. The sequence features were elaborated based on the combination of next-generation sequencing (NGS) and multidimensional bioinformatics analysis.ResultsThe 16 high-frequency missense mutations, changes of stop codon mutation, clustering, and random forest models based on quasispecies features demonstrated the significant discrepancy power between HBsAg+/HBsAb+ and HBsAg+/HBsAb− in CHB and HCC, respectively. The immunogenicity for cytotoxic T lymphocyte (CTL) epitope Se and antigenicity for the major hydrophilic region (MHR) were both reduced in HBsAg+/HBsAb+ patients (CTL Se: p < 0.0001; MHR: p = 0.0216). Different mutation patterns were observed between HBsAg+/HBsAb+ patients with CHB and with HCC. Especially, mutations in antigenic epitopes, such as I126S in CHB and I126T in HCC, could impact the conformational structure and alter the antigenicity/immunogenicity of HBsAg.ConclusionBased on NGS and bioinformatics analysis, this study indicates for the first time that point mutations and quasispecies diversities of HBV s gene could alter the MHR antigenicity and CTL Se immunogenicity and could contribute to the concurrent HBsAg+/HBsAb+ with different features in HCC and CHB. Our findings might renew the understanding of this special serological profile and benefit the clinical management in HBV-related diseases.

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Coexistence of low levels of HBsAg and high levels of anti-HBs may increase risk of hepatocellular carcinoma in chronic hepatitis B patients with high HBV load

Cited by 11 publications

References 21 publications

Decreased hepatitis B virus vaccine response among HIV-positive infants compared with HIV-negative infants in Botswana

Decreased hepatitis B virus vaccine response among HIV-positive infants compared with HIV-negative infants in Botswana

Paradoxical HBsAg and anti-HBs coexistence among Chronic HBV Infections: Causes and Consequences

The Impact of HBV Quasispecies Features on Immune Status in HBsAg+/HBsAb+ Patients With HBV Genotype C Using Next-Generation Sequencing

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